| 1. |
- Alzuhairi, Karam Sadoon, et al.
(författare)
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Sub-acute cardiac magnetic resonance to predict irreversible reduction in left ventricular ejection fraction after ST-segment elevation myocardial infarction : A DANAMI-3 sub-study
- 2020
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 301, s. 215-219
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). Methods and results: A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47–36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07–50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27–47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83–328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. Conclusion: Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization.
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| 2. |
- Engstrøm, Thomas, et al.
(författare)
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Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients : A phase 2 randomised clinical trial
- 2018
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 104:19, s. 1593-1599
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. Methods: In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. Results: From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. Conclusions: Administration of danegaptide to patients with STEMI did not improve myocardial salvage. Trial registration number: NCT01977755; Pre-results.
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| 3. |
- Iversen, Anne Kristine Servais, et al.
(författare)
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A simple clinical assessment is superior to systematic triage in prediction of mortality in the emergency department
- 2019
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Ingår i: Emergency Medicine Journal. - : BMJ. - 1472-0213 .- 1472-0205. ; 36:2, s. 66-71
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Tidskriftsartikel (refereegranskat)abstract
- Objective To compare the Danish Emergency Process Triage (DEPT) with a quick clinical assessment (Eyeball triage) as predictors of short-term mortality in patients in the emergency department (ED).Methods The investigation was designed as a prospective cohort study conducted at North Zealand University Hospital. All patient visits to the ED from September 2013 to December 2013 except minor injuries were included. DEPT was performed by nurses. Eyeball triage was a quick non-systematic clinical assessment based on patient appearance performed by phlebotomists. Both triage methods categorised patients as green (not urgent), yellow, orange or red (most urgent). Primary analysis assessed the association between triage level and 30-day mortality for each triage method. Secondary analyses investigated the relation between triage level and 48-hour mortality as well as the agreement between DEPT and Eyeball triage.Results A total of 6383 patient visits were included. DEPT was performed for 6290 (98.5%) and Eyeball triage for 6382 (~100%) of the patient visits. Only patients with both triage assessments were included. The hazard ratio (HR) for 48-hour mortality for patients categorised as yellow was 0.9 (95% CI 0.4 to 1.9) for DEPT compared with 4.2 (95% CI 1.2 to 14.6) for Eyeball triage (green is reference). For orange the HR for DEPT was 2.2 (95% CI 1.1 to 4.4) and 17.1 (95% CI 5.1 to 57.1) for Eyeball triage. For red the HR was 30.9 (95% CI 12.3 to 77.4) for DEPT and 128.7 (95% CI 37.9 to 436.8) for Eyeball triage. For 30-day mortality the HR for patients categorised as yellow was 1.7 (95% CI 1.2 to 2.4) for DEPT and 2.4 (95% CI 1.6 to 3.5) for Eyeball triage. For orange the HR was 2.6 (95% CI 1.8 to 3.6) for DEPT and 7.6 (95% CI 5.1 to 11.2) for Eyeball triage, and for red the HR was 19.1 (95% CI 10.4 to 35.2) for DEPT and 27.1 (95% CI 16.9 to 43.5) for Eyeball triage. Agreement between the two systems was poor (kappa 0.05).Conclusion Agreement between formalised triage and clinical assessment is poor. A simple clinical assessment by phlebotomists is superior to a formalised triage system to predict short-term mortality in ED patients.
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| 4. |
- Kyhl, Kasper, et al.
(författare)
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Complete Revascularization Versus Culprit Lesion Only in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease : A DANAMI-3–PRIMULTI Cardiac Magnetic Resonance Substudy
- 2019
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Ingår i: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798. ; 12:8, s. 721-730
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to evaluate the effect of fractional flow reserve (FFR)–guided revascularization compared with culprit-only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) on infarct size, left ventricular (LV), function, LV remodeling, and the presence of nonculprit infarctions. Background: Patients with STEMI with multivessel disease might have improved clinical outcomes after complete revascularization compared with PCI of the infarct-related artery only, but the impact on infarct size, LV function, and remodeling as well as the risk for periprocedural infarction are unknown. Methods: In this substudy of the DANAMI-3 (Third Danish Trial in Acute Myocardial Infarction)–PRIMULTI (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization) randomized trial, patients with STEMI with multivessel disease were randomized to receive either complete FFR-guided revascularization or PCI of the culprit vessel only. The patients underwent cardiac magnetic resonance imaging during index admission and at 3-month follow-up. Results: A total of 280 patients (136 patients with infarct-related and 144 with complete FFR-guided revascularization) were included. There were no differences in final infarct size (median 12% [interquartile range: 5% to 19%] vs. 11% [interquartile range: 4% to 18%]; p = 0.62), myocardial salvage index (median 0.71 [interquartile range: 0.54 to 0.89] vs. 0.66 [interquartile range: 0.55 to 0.87]; p = 0.49), LV ejection fraction (mean 58 ± 9% vs. 59 ± 9%; p = 0.39), and LV end-systolic volume remodeling (mean 7 ± 22 ml vs. 7 ± 19 ml; p = 0.63). New nonculprit infarction occurring after the nonculprit intervention was numerically more frequent among patients treated with complete revascularization (6 [4.5%] vs. 1 [0.8%]; p = 0.12). Conclusions: Complete FFR-guided revascularization in patients with STEMI and multivessel disease did not affect final infarct size, LV function, or remodeling compared with culprit-only PCI.
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| 5. |
- Laursen, Peter Nørkjær, et al.
(författare)
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Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study
- 2018
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 204, s. 128-138
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Tidskriftsartikel (refereegranskat)abstract
- Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. Results: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P <.001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P <.001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all <.001). Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.
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| 6. |
- Madsen, Jasmine Melissa, et al.
(författare)
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Clinical outcomes of no stenting in patients with ST-segment elevation myocardial infarction undergoing deferred primary percutaneous coronary intervention
- 2022
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Ingår i: EuroIntervention. - 1774-024X. ; 18:6, s. 482-491
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Tidskriftsartikel (refereegranskat)abstract
- Background: ST-segment elevation myocardial infarction (STEMI) is treated with stenting, but the underlying stenosis is often not severe, and stenting may potentially be omitted. Aims: The aim of the study was to investigate outcomes of patients with STEMI treated with percutaneous coronary intervention (PCI) without stenting. Methods: Patients were identified through the DANAMI-3-DEFER study. Stenting was omitted in the patients with stable flow after initial PCI and no significant residual stenosis on the deferral procedure, who were randomised to deferred stenting. These patients were compared to patients randomised to conventional PCI treated with immediate stenting. The primary endpoint was a composite of all-cause mortality, recurrent myocardial infarction (MI), and target vessel revascularisation (TVR). Results: Of 603 patients randomised to deferred stenting, 84 were treated without stenting, and in patients randomised to conventional PCI (n=612), 590 were treated with immediate stenting. Patients treated with no stenting had a median stenosis of 40%, median vessel diameter of 2.9 mm, and median lesion length of 11.4 mm. During a median follow-up of 3.4 years, the composite endpoint occurred in 14% and 16% in the no and immediate stenting groups, respectively (unadjusted hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.48-1.60; p=0.66). The association remained non-significant after adjusting for confounders (adjusted HR 0.53, 95% CI: 0.22-1.24; p=0.14). The rates of TVR and recurrent MI were 2% vs 4% (p=0.70) and 4% vs 6% (p=0.43), respectively. Conclusions: Patients with STEMI, with no significant residual stenosis and stable flow after initial PCI, treated without stenting, had comparable event rates to patients treated with immediate stenting.
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| 7. |
- Madsen, Jasmine Melissa, et al.
(författare)
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Comparison of Effect of Ischemic Postconditioning on Cardiovascular Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention With Versus Without Thrombectomy
- 2022
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 166, s. 18-24
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Tidskriftsartikel (refereegranskat)abstract
- In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy.
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| 8. |
- Mohammad, Moman A., et al.
(författare)
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Usefulness of High Sensitivity Troponin T to Predict Long-Term Left Ventricular Dysfunction After ST-Elevation Myocardial Infarction
- 2020
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 134, s. 8-13
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Tidskriftsartikel (refereegranskat)abstract
- Guidelines recommend the use of transthoracic echocardiography (TTE) and clinical scores to risk stratify patients after ST-elevation myocardial infarction (STEMI). High sensitivity troponin T (hs-cTnT) is predictive of outcome after STEMI but the predictive value of hs-cTnT relative to other risk assessment tools has not been established. We aimed to compare the predictive value of hs-cTnT to other risk assessment tools in patients with STEMI. A subset of 578 patients with STEMI were included in this post-hoc study from the Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction trial. Patients underwent cardiac magnetic resonance imaging (CMR) during index hospitalization as well as TTE at 1 year after their STEMI. The predictive value of hs-cTnT was compared with CKMB, infarct size (IS)/left ventricular ejection fraction (LVEF) assessed with CMR, LVEF assessed at discharge with TTE and the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) risk-scores. The primary outcome was LV systolic dysfunction defined as LVEF ≤40% after 1 year on TTE. The area under the receiver operating characteristic curve analyses showed no significant difference between hs-cTnT and early CMR-assessed IS or LVEF in predicting subsequent LVEF ≤40%. Area under the curve for hs-cTnT was 0.82, 0.85 for IS (p = 0.22), and 0.87 for LVEF (p = 0.23). For predischarge TTE-assessed LVEF, the value was 0.85 (p = 0.45), 0.63 for creatine kinase-MB (p <0.001), 0.61 for the GRACE score (p <0.001), and 0.70 for the TIMI score (p = 0.02). A peak hs-cTnT value <3,500 ng/L ruled out LVEF ≤40% with probability of 98%. In conclusion, in patients presenting with STEMI undergoing PCI, hs-cTnT level strongly predicted long-term LV dysfunction and could be used as a clinical risk stratification tool to identify patients at high risk of progressing to LV dysfunction due to its general availability and high-predictive accuracy.
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| 9. |
- Nepper-Christensen, Lars, et al.
(författare)
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Benefit From Reperfusion With Primary Percutaneous Coronary Intervention Beyond 12 Hours of Symptom Duration in Patients With ST-Segment-Elevation Myocardial Infarction
- 2018
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Ingår i: Circulation. Cardiovascular Interventions. - 1941-7632. ; 11:9, s. 006842-006842
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Guidelines recommend primary percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI) presenting ≥12 hours of symptom onset in the presence of ongoing ischemia. However, data supporting this recommendation are limited. We evaluated the effect of primary PCI on reperfusion success, using cardiac magnetic resonance, in STEMI patients with signs of ongoing ischemia presenting 12 to 72 hours after symptom onset compared with STEMI patients presenting <12 hours.METHODS AND RESULTS: We included 865 STEMI patients who underwent cardiac magnetic resonance just after index PCI and 3 months later. Despite equal area at risk (34±12% versus 33±12%; P=0.370), patients presenting late (n=58) had larger final infarct size (13% [interquartile range, 9-24] versus 11% [interquartile range, 4-19]; P=0.037) and smaller myocardial salvage index (0.58 [interquartile range, 0.39-0.71] versus 0.65 [interquartile range, 0.49-0.84]; P=0.021) compared with patients presenting <12 hours after symptom onset (n=807). However, 65% of late-presenting patients achieved substantial myocardial salvage ≥0.50, and area under the curve for symptom onset to PCI as predictor of a myocardial salvage index ≥0.50 was poor (0.58 [95% CI, 0.53-0.63]; P<0.001). In addition, final infarct size, salvage index and left ventricular function correlated weakly with duration from symptom onset to primary PCI ( R2 values <0.05).CONCLUSIONS: STEMI patients with signs of ongoing ischemia treated with primary PCI 12 to 72 hours after symptom onset had less myocardial salvage and developed larger infarcts. However, a large proportion achieved substantial myocardial salvage indicating a benefit from primary PCI in late-presenting patients.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01435408 and NCT01960933.
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| 10. |
- Nepper-Christensen, Lars, et al.
(författare)
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Clinical outcome following late reperfusion with percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction
- 2021
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Ingår i: European Heart Journal: Acute Cardiovascular Care. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 10:5, s. 523-531
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Tidskriftsartikel (refereegranskat)abstract
- Background: Up to 40% of patients with ST-segment elevation myocardial infarction (STEMI) present later than 12 hours after symptom onset. However, data on clinical outcomes in STEMI patients treated with primary percutaneous coronary intervention (PCI) ≥12 hours after symptom onset are non-existent. We evaluated the association between primary PCI performed later than 12 hours after symptom onset and clinical outcomes in a large all-comer contemporary STEMI cohort. Methods: All STEMI patients treated with primary PCI in eastern Denmark from November 2009 to November 2016 were included and stratified by timing of the PCI. The combined clinical endpoint of all-cause mortality and hospitalisation for heart failure was identified from nationwide Danish registries. Results: We included 6674 patients: 6108 (92%) were treated <12 hours and 566 (8%) were treated ≥12 hours after symptom onset. During a median follow-up period of 3.8 (interquartile range 2.3-5.6) years, 30-day, one-year and long-term cumulative rates of the combined endpoint were 11%, 17% and 25% in patients treated <12 hours and 21%, 29% and 37% in patients treated ≥12 hours after symptom onset (P > 0.001 for all). Late presentation was independently associated with an increased risk of an adverse clinical outcome (hazard ratio 1.42, 95% confidence interval 1.22-1.66; P < 0.001). Conclusions: Increasing duration from symptom onset to primary PCI was associated with an increased risk of an adverse clinical outcome in patients with STEMI, especially when the delay exceeded 12 hours.
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| 11. |
- Nepper-Christensen, Lars, et al.
(författare)
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Impact of diagnostic ECG-to-wire delay in STEMI patients treated with primary PCI : A DANAMI-3 substudy
- 2018
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Ingår i: EuroIntervention. - 1774-024X. ; 14:6, s. 700-707
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We aimed to evaluate the impact of delay from diagnostic pre-hospital electrocardiogram (ECG) to wiring of the infarct-related vessel (ECG-to-wire) >120 minutes on cardiovascular magnetic resonance (CMR) markers of reperfusion success and clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results: We included 1,492 patients in the analyses of clinical outcome. CMR was performed in 748 patients to evaluate infarct size and myocardial salvage. In total, 304 patients (20%) had ECG-to-wire >120 minutes, which was associated with larger acute infarct size (18% [interquartile range (IQR), 10-28] vs. 15% [8-24]; p=0.022) and smaller myocardial salvage (0.42 [IQR 0.28-0.57] vs. 0.50 [IQR 0.34-0.70]; p=0.002). However, 33% of the patients with ECG-to-wire >120 minutes still had a substantial myocardial salvage ≥0.50. In a multivariable analysis, ECG-to-wire >120 minutes was associated with an increased risk of all-cause mortality and heart failure (hazard ratio 1.61, 95% confidence interval [CI] 1.14-2.26, p=0.007). Conclusions: ECG-to-wire >120 minutes was associated with larger infarct size, smaller myocardial salvage and a poorer clinical outcome in STEMI patients transferred for primary percutaneous coronary intervention. However, myocardial salvage was still substantial in one third of patients treated beyond 120 minutes of delay.
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| 12. |
- Rasmussen, Rasmus V, et al.
(författare)
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One-year mortality in coagulase-negative Staphylococcus and Staphylococcus aureus infective endocarditis.
- 2009
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 41:6-7, s. 456-61
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate in-hospital mortality and 12-month mortality in patients with coagulase-negative Staphylococcus (CoNS) compared to Staphylococcus aureus (S. aureus) infective endocarditis (IE). We used a prospective cohort study of 66 consecutive CoNS and 170 S. aureus IE patients, collected at 2 tertiary university hospitals in Copenhagen (Denmark) and at 1 tertiary university hospital in Gothenburg (Sweden). Median (range) C-reactive protein at admission was higher in patients with S. aureus IE (150 mg/l (1-521) vs 94 mg/l (6-303); p<0.001), which may suggest a more serous infection. CoNS was associated with prosthetic valve IE (49% vs 24%; p<0.001) and median diagnostic delay was longer in CoNS IE patients (20 d (0-232) vs 9 d (0-132); p<0.001). In-hospital mortality was equally high in both groups but 25% of the CoNS IE patients had died after 1 y compared to 39% of patients with S. aureus IE (p =0.05). In conclusion, CoNS IE was associated with a long diagnostic delay and high in-hospital mortality, whereas post-discharge prognosis was better in this group of patients compared to patients with IE due to S. aureus.
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| 13. |
- Andreasen, Charlotte, et al.
(författare)
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Incidence of Ischemic Stroke in Individuals with and without Aortic Valve Stenosis : A Danish Retrospective Cohort Study
- 2020
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Ingår i: Stroke. - 0039-2499. ; 51:1, s. 1364-1371
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose - Aortic valve stenosis may lead to atrial and ventricular remodeling, predisposes to atrial fibrillation, and may also be an independent risk factor of ischemic stroke. However, information on stroke rates among persons with aortic valve stenosis are sparse. We aimed to determine the incidence rates and relative risks of ischemic stroke in individuals with diagnosed aortic valve stenosis compared with age- and sex-matched controls. Methods - All patients with incident aortic valve stenosis aged >18 years (n=79 310) and age- and sex-matched controls were identified using the Danish nationwide registries (1997-2017). Incidence rates per 1000 person-years (PY) and multivariable adjusted hazard ratios with 95% CIs were reported. Results - In total, 873 373 individuals (median age 77 years, 51.5% men, 9.1% with aortic valve stenosis) were included. Ischemic stroke occurred in 70 205 (8.0%) individuals during 4 880 862 PY of follow-up. Incidence rates of ischemic stroke were 13.3/1000 PY among the controls compared with 30.4/1000 PY in patients with aortic valve stenosis, corresponding to a hazard ratio of 1.31 (95% CI, 1.28-1.34). In all age-groups, the incidence rates and relative risks were significantly increased in patients with aortic valve stenosis compared with controls, but the relative risk was greater for younger individuals (eg, age group, 18-45 years: hazard ratio, 5.94 [95% CI, 4.10-8.36]). In patients with aortic valve stenosis above 65 years of age, the risk of ischemic stroke was markedly lower after aortic valve replacement (30.3 versus 19.6/1000 PY before and after valve replacement). Among people with atrial fibrillation the incidence rate of ischemic stroke was 1.5 times higher when aortic valve stenosis was present (33.0/1000 PY versus 49.9/1000 PY). Conclusions - People with aortic valve stenosis have a significantly increased risk of ischemic stroke compared with age- and sex-matched controls. Future studies are warranted to explore whether antithrombotic therapy may be beneficial in some individuals.
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| 14. |
- Andrikopoulos, Petros, et al.
(författare)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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| 15. |
- Bjørnsbo, Kirsten Schroll, et al.
(författare)
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Protocol for the combined cardiometabolic deep phenotyping and registry-based 20-year follow-up study of the Inter99 cohort
- 2024
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Ingår i: BMJ Open. - 2044-6055. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50–80 years old Inter99 participants. Methods and analysis The Inter99 cohort comprises individuals aged 30–60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbidities. Ethics and dissemination The study was approved by the Medical Ethics Committee, Capital Region, Denmark (H-20076231) and by the Danish Data Protection Agency through the Capital Region of Denmark’s registration system (P-2020-1074). Informed consent will be obtained before examinations. Findings will be disseminated in peer-reviewed journals, at conferences and via presentations to stakeholders, including patients and public health policymakers.
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| 16. |
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| 17. |
- Christiansen, Mia N., et al.
(författare)
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Age-specific Trends in Incidence, Mortality and Comorbidities of Heart Failure in Denmark 1995-2012
- 2017
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Ingår i: Circulation. - 0009-7322. ; 135:13, s. 1214-1223
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND—: The cumulative burden and importance of cardiovascular risk factors have changed over the last decades. Specifically, obesity rates have increased among younger people, whereas cardiovascular health has improved in the elderly. Little is known regarding how these changes have impacted the incidence and the mortality rates of heart failure. Therefore, we aimed to investigate the age-specific trends in the incidence and 1-year mortality rates following a first time diagnosis of heart failure in Denmark between 1995 and 2012. METHODS—: We included all Danish individuals over the age of 18 years with a first-time in-hospital diagnosis of heart failure. Data was collected from 3 nationwide Danish registries. Annual incidence rates of heart failure and 1-year standardized mortality rates were calculated under the assumption of a Poisson distribution. RESULTS—: We identified 210,430 individuals with a first-time diagnosis of heart failure between 1995 and 2012; the annual incidence rates per 10,000 person-years declined among older individuals (rates in 1995 vs. 2012: 164 vs. 115 in >74 years, 63 vs. 35 in 65-74 years, and 20 vs. 17 in 55-64 years, p<0.0001 for all) but increased among the younger (0.4 vs. 0.7 in 18-34 years, 1.3 vs. 2.0 in 35-44 years, and 5.0 vs. 6.4 in 45-54 years, p<0.0001 for all). The proportion of patients with incident heart failure below 51 years doubled from 3% in 1995 to 6% in 2012 (p<0.0001). Sex- and age-adjusted incidence rate ratios for 2012 vs. 1996 were 0.69 (95%CI 0.67-0.71; p <0.0001) among people >50 years, and 1.52 (95%CI 1.33-1.73; p<0.0001) among individuals ≤50 years; it remained essentially unchanged upon additional adjustment for diabetes, ischemic heart disease, and hypertension. Standardized 1-year mortality rates declined for middle-aged patients with heart failure but remained constant for younger (<45 years) and elderly (≥65 years). The prevalence of comorbidities (including diabetes, hypertension, and atrial fibrillation) increased, especially in younger patients with heart failure. CONCLUSIONS—: Over the last two decades, the incidence of heart failure in Denmark declined among older (>50 years), but increased among younger (≤50 years) individuals. These observations may portend a rising burden of heart failure in the community.
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| 18. |
- Christiansen, Mia Nielsen, et al.
(författare)
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Prevalence of heart failure and other risk factors among first-degree relatives of women with peripartum cardiomyopathy
- 2019
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:14, s. 1057-1062
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Peripartum cardiomyopathy (PPCM) is a rare disease carrying a risk of death and chronic heart failure.It is unknown if women with PPCM have a family history of heart failure. We investigated the prevalence of heart failure and hypertension in first-degree relatives to women with PPCM. Methods: A cohort of 61 women with PPCM was identified through the nationwide Danish registers from 2005 to 2014, and each individual diagnosis of PPCM was validated through review of patient records. We excluded 13 women due to lack of data on relatives. In a case-control design, the 48 remaining women were matched (on age, year of childbirth, parity and number of siblings) to 477 birth-giving Danish women without heart failure. We obtained information on first-degree relatives (parents and siblings) through the National Danish Registers. Results: The cohort of 48 women with PPCM had a mean age of 31 years (SD 6). The prevalence of heart failure in any first-degree relative was higher in women with PPCM, compared with controls (23% vs 10%, p=0.011). A first-degree relative with any cardiovascular diagnosis was not more frequent in women with PPCM versus controls (77% vs 70%, p=0.280), but for siblings only, any cardiovascular diagnosis was more frequent in siblings to women with PPCM (29% vs 16%, p=0.026). Conclusion: Having a first-degree relative with heart failure was significantly more frequent in a cohort of validated PPCM cases than in controls, supporting the notion of shared aetiology between PPCM and other forms of heart failure.
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| 19. |
- Dewan, Pooja, et al.
(författare)
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Heart failure with reduced ejection fraction: comparison of patient characteristics and clinical outcomes within Asia and between Asia, Europe and the Americas.
- 2019
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 21:5, s. 577-587
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Tidskriftsartikel (refereegranskat)abstract
- Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world.We pooled two, large, global trials, with similar design, in 13174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0-63.9years) than in Western Europe (67.9years) and North America (66.6years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100patient-years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan.Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences.
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| 20. |
- Dewan, Pooja, et al.
(författare)
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Impact of multimorbidity on mortality in heart failure with reduced ejection fraction: which comorbidities matter most? An analysis of PARADIGM-HF and ATMOSPHERE
- 2023
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Ingår i: European Journal of Heart Failure. - 1388-9842 .- 1879-0844. ; 25:5, s. 687-97
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Multimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure (HF). How risk related to comorbidities compares at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels. Methods and results: Using two clinical trials in HF–the Prospective comparison of ARNI (Angiotensin Receptor–Neprilysin Inhibitor) with ACEI (Angiotensin-Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and morbidity in HF trial (PARADIGM-HF) and the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure trials (ATMOSPHERE)–we identified the 10 most common comorbidities and examined 45 possible pairs. We calculated population attributable fractions (PAF) for all-cause death and relative excess risk due to interaction with Cox proportional hazard models. Of 15 066 patients in the study, 14 133 (93.7%) had at least one and 11 867 (78.8%) had at least two of the 10 most prevalent comorbidities. The greatest individual risk among pairs was associated with peripheral artery disease (PAD) in combination with stroke (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.28–2.33) and anaemia (HR 1.71; 95% CI 1.39–2.11). The combination of chronic kidney disease (CKD) and hypertension had the highest PAF (5.65%; 95% CI 3.66–7.61). Two pairs demonstrated significant synergistic interaction (atrial fibrillation with CKD and coronary artery disease, respectively) and one an antagonistic interaction (anaemia and obesity). Conclusions: In HF, the impact of multimorbidity differed at the individual patient and population level, depending on the prevalence of and the risk related to each comorbidity, and the interaction between individual comorbidities. Patients with coexistent PAD and stroke were at greatest individual risk whereas, from a population perspective, coexistent CKD and hypertension mattered most.
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| 21. |
- Dewan, Pooja, et al.
(författare)
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Sex-Related Differences in Heart Failure With Preserved Ejection Fraction.
- 2019
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Ingår i: Circulation. Heart failure. - 1941-3297. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- To describe characteristics and outcomes in women and men with heart failure with preserved ejection fraction.Baseline characteristics (including biomarkers and quality of life) and outcomes (primary outcome: composite of first heart failure hospitalization or cardiovascular death) were compared in 4458 women and 4010 men enrolled in CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) (EF≥45%), I-Preserve (Irbesartan in heart failure with Preserved ejection fraction), and TOPCAT-Americas (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial).Women were older and more often obese and hypertensive but less likely to have coronary artery disease or atrial fibrillation. Women had more symptoms and signs of congestion and worse quality of life. Despite this, the risk of the primary outcome was lower in women (hazard ratio, 0.80 [95% CI, 0.73-0.88]), as was the risk of cardiovascular death (hazard ratio, 0.70 [95% CI, 0.62-0.80]), but there was no difference in the rate for first hospitalization for heart failure (hazard ratio, 0.92 [95% CI, 0.82-1.02]). The lower risk of cardiovascular death in women, compared with men, was in part explained by a substantially lower risk of sudden death (hazard ratio, 0.53 [0.43-0.65]; P<0.001). E/A ratio was lower in women (1.1 versus 1.2).There are significant differences between women and men with heart failure with preserved ejection fraction. Despite worse symptoms, more congestion, and lower quality of life, women had similar rates of hospitalization and better survival than men. Their risk of sudden death was half that of men.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00853658, NCT01035255.
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| 22. |
- Docherty, Kieran F, et al.
(författare)
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Effects of dapagliflozin in DAPA-HF according to background heart failure therapy.
- 2020
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:25, s. 2379-2392
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Tidskriftsartikel (refereegranskat)abstract
- In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether this benefit was consistent in relation to background HF therapy.In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and <50% of target dose). We analysed the primary composite endpoint of cardiovascular death or a worsening HF event. Most randomized patients (n=4744) were treated with a diuretic (84%), renin-angiotensin system (RAS) blocker (94%), and BB (96%); 52% of those taking a BB and 38% taking a RAS blocker were treated with ≥50% of the recommended dose. Overall, the dapagliflozin vs. placebo hazard ratio (HR) was 0.74 [95% confidence interval (CI) 0.65-0.85] for the primary composite endpoint (P<0.0001). The effect of dapagliflozin was consistent across all subgroups examined: the HR ranged from 0.57 to 0.86 for primary endpoint, with no significant randomized treatment-by-subgroup interaction. For example, the HR in patients taking a RAS blocker, BB, and MRA at baseline was 0.72 (95% CI 0.61-0.86) compared with 0.77 (95% CI 0.63-0.94) in those not on all three of these treatments (P-interaction 0.64).The benefit of dapagliflozin was consistent regardless of background therapy for HF.
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| 23. |
- Docherty, Kieran F, et al.
(författare)
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Relationship between heart rate and outcomes in patients in sinus rhythm or atrial fibrillation with heart failure and reduced ejection fraction.
- 2020
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 22:3, s. 528-538
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the relationship between heart rate and outcomes in heart failure and reduced ejection fraction (HFrEF) patients in sinus rhythm (SR) and atrial fibrillation (AF) adjusting for natriuretic peptide concentration, a powerful prognosticator.Of 13562 patients from two large HFrEF trials, 10113 (74.6%) were in SR and 3449 (25.4%) in AF. The primary endpoint was the composite of cardiovascular death or heart failure hospitalization. Heart rate was analysed as a categorical (tertiles, T1-3) and continuous variable (per 10bpm), separately in patients in SR and AF. Outcomes were adjusted for prognostic variables, including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and also examined using change from baseline heart rate to 1year (≤-10bpm, ≥+10bpm, <±10bpm). SR patients with a higher heart rate had worse symptoms and quality of life, more often had diabetes and higher NT-proBNP concentrations. They had higher risk of the primary endpoint [T3 vs. T1 adjusted hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.35-1.66; P<0.001; per 10bpm: 1.12, 95% CI 1.09-1.16; P<0.001]. In SR, heart rate was associated with a relatively higher risk of pump failure than sudden death (adjusted HR per 10bpm 1.17, 95% CI 1.09-1.26; P<0.001 vs. 1.07, 95% CI 1.02-1.13; P=0.011). Heart rate was not predictive of any outcome in AF.In HFrEF, an elevated heart rate was an independent predictor of adverse cardiovascular outcomes in patients in SR, even after adjustment for NT-proBNP. There was no relationship between heart rate and outcomes in AF.ClinicalTrials.gov Identifiers NCT01035255 and NCT00853658.
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| 24. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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| 25. |
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